Introduction Most anal cancers are associated with HPV, particularly HPV 16. The incidence of anal cancer is increased among men who have sex with men (MSM) compared with the general population. Screening and treatment of anal intraepithelial neoplasia (AIN), the anal cancer precursor, are not yet standard of care, and prevention efforts are needed to reduce the incidence of anal cancer. We tested the quadrivalent HPV vaccine to determine its ability to reduce the incidence of AIN/anal cancer.

Methods 598 MSM aged 16–26 years with five or fewer lifetime sex partners were randomised to receive vaccine or placebo at enrolment, month 2 and month 6. Subjects underwent detailed anogenital exams and HPV sampling from the penis, scrotum, perineal/perianal and anal canal at enrolment, month 7 and at 6-month intervals afterwards. Efficacy analyses were performed in a per-protocol (PPE) population (sero-negative and DNA-negative from day 1 through month 7 to the relevant vaccine HPV type) and in all enrolees in an intent-to treat (ITT) analysis. Median follow-up of the PPE population was 2.5 years (post-dose 3).

Results Vaccine efficacy against HPV 6/11/16/18-related AIN and anal cancer in the PPE population was 77.5% (95% CI 39.6 to 93.3) (5 vaccine cases vs 24 placebo cases). Efficacy against high-grade AIN (AIN 2+) was 74.9% (95% CI 8.8 to 95.4). In the ITT population the efficacy was 50.3% (95% CI 25.7 to 67.2) and 54.2% (95% CI 18.0 to 75.3), respectively. No anal cancer was seen in either treatment group.

Conclusions These results demonstrate that the quadrivalent HPV vaccine is efficacious in preventing AIN related to HPV 6/11/16/18 in MSM subjects naïve to vaccine HPV types at enrolment, as well as in an ITT population. The quadrivalent HPV vaccine may be a useful measure to reduce the incidence of anal disease in at-risk populations.